CN101820754A - Compositions and methods for enhancing cognitive function - Google Patents

Compositions and methods for enhancing cognitive function Download PDF

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Publication number
CN101820754A
CN101820754A CN200880110329A CN200880110329A CN101820754A CN 101820754 A CN101820754 A CN 101820754A CN 200880110329 A CN200880110329 A CN 200880110329A CN 200880110329 A CN200880110329 A CN 200880110329A CN 101820754 A CN101820754 A CN 101820754A
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animal
composition
mcts
lcpufa
norc
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潘元龙
M·沃尔德伦
B·T·拉尔森
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Nestec SA
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Societe dAssistance Technique pour Produits Nestle SA
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/20Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • A23K20/158Fatty acids; Fats; Products containing oils or fats
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K50/00Feeding-stuffs specially adapted for particular animals
    • A23K50/40Feeding-stuffs specially adapted for particular animals for carnivorous animals, e.g. cats or dogs
    • A23K50/42Dry feed
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K50/00Feeding-stuffs specially adapted for particular animals
    • A23K50/40Feeding-stuffs specially adapted for particular animals for carnivorous animals, e.g. cats or dogs
    • A23K50/48Moist feed
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
    • A61K31/198Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/20Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/201Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having one or two double bonds, e.g. oleic, linoleic acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/20Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/202Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/21Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/21Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/3533,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355Tocopherols, e.g. vitamin E
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365Lactones
    • A61K31/375Ascorbic acid, i.e. vitamin C; Salts thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/04Sulfur, selenium or tellurium; Compounds thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56Materials from animals other than mammals
    • A61K35/60Fish, e.g. seahorses; Fish eggs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/26Psychostimulants, e.g. nicotine, cocaine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Abstract

The invention provides compositions comprising one or more long chain polyunsaturated fatty acids, nitric oxide releasing compounds, and medium chain triglycerides and methods for using such compositions for enhancing cognitive function, reducing or preventing a decline of social interaction, reducing or preventing age- related behavioral changes, increasing trainabihty, maintaining optimal brain function, facilitating learning and memory, reducing memory loss, retarding brain aging, preventing or treating strokes, and preventing or treating dementia in an animal Preferably, the compositions are food compositions useful for enhancing cognitive function in humans and companion animals.

Description

Be used to strengthen the composition and the method for cognitive function
The cross reference of related application
The application requires the priority of the U.S. Provisional Patent Application 60/997,665 of submission on October 4th, 2007, and its disclosure is incorporated herein by reference.
Background of invention
Invention field
Generally, the present invention relates to be used to strengthen the composition and the method for cognitive function, particularly comprise the composition of long-chain polyunsaturated fatty acid, nitric oxide release property compound and medium chain triglyceride and they strengthen the application of cognitive function in animal.
Description of Related Art
The Cognitive function damage of often suffering from some degree animal old or aging.The variation that often observes comprises with the relevant variation with the age in the decline of cognitive function of change of age and brain morphology and the cerebrovascular function, for example, and brain aging.Age is correlated with or the cognitive impairment relevant with the age itself can show as various ways, for example short term memory loss, learning ability decline, pace of learning decline, decreased attention, locomitivity decline and/or dementia etc.In some cases, these cognitive concrete causes of disease that descend are not quite clear.In other cases, cognitive impairment is derived from cognitive disorders, obstacle or syndromic outbreak or development, for example Alzheimer disease (AD).The known cognition relevant with the age descends to being different from AD and can being independent of AD and takes place.
The animal model of cognitive impairment has promoted to comprise the research of this class illness of its physiology, neurology, anatomy and pathology greatly.Dog is effective animal pattern, and they have confirmed that cognition relevant with the age in learning and memory descends, and it changes (people such as Adams B, 2000a according to the function of cognition work; People such as Chan AD, 2002; People such as Su M-Y, 1998 and people such as Tapp PD, 2003).Although because dog is studied from its right angle its cognitive decline as the effect of companion animals is useful, but viewed decline reflected seen in the mankind to the cognition relevant this fact that descends with the age, make this research more valuable (people such as Adams B, 2000b).Old dog develops and the relevant neuropathology of pathological conditions that arrives seen in the people of usual aging and the AD patient, as amyloid-beta (Cotman CW and Berchtold, 2002; With people such as Cummings BJ, 1996).But dog does not confirm each mark of AD, does not particularly observe the neurofibrillary tangles (people such as Dimakopoulos AC, 2002) that contains Protein tau.Therefore, the illness of dog is different, is called as dog cognition dysfunction syndrome (CCDS).
Healthy dog and unsound dog for example those diagnosis dog of suffering from CCDS can exist progressive cognitive impairment and neuropathology to change people such as (, 1983) London ED clinically.In addition, Shuai Lao dog and those diagnosis dog of suffering from CCDS demonstrates the various actions obstacle.For example, they may not can be reacted to their name or familiar order, may in the environment of being familiar with, get lost or fascination, may their owner or guest no longer be welcome or react, may show movable minimizing the on daytime, possible pitch of the laps is walked, and may hide emotion, and may lose urinate control or defecation control.
Relevant cognition decline of age and impaired glucose metabolism are relevant people such as (, 1997) Finch CE.The main energy sources of healthy animal or mammiferous brain is a glucose.Impaired glucose metabolism can reduce ability people such as (, 1998) Munch G of cell repair and opposing oxidative damage.Neurone loss that accompanies with it and morphological abnormalities show that the brain function that has promoted senior people descends.Thereby impaired glucose metabolism can be in brain produce power lack, and can cause neuronic loss and morphologic change (Hoyer S., 1990) in the brain.
The patient of Alzheimer disease also shows glucose metabolism and descends.The research of positron emission tomography has shown the reduction (people such as Drzezga A, 2005 and people such as Small GW, 2000) of brain glucose level.Descend really that cutter system does not also fully understand although the gentle glucose metabolism of G/W occurs, but the reduction of neuropathology incident such as oxidative stress, nerve cell death and acetylcholine, ATP and cholesterol levels, all with brain in the decline relevant (people such as Swaab, 1998) of energy and glucose metabolism.
According to a kind of hypothesis, except the influence that glucose metabolism changes, the reduction of the RBF of brain has also promoted people's cognition to descend and dementia people such as (, 2003) Wardlaw JM.Local cerebral blood volume is subjected to the influence (people such as Split A, 2005 and people such as Petrella JR, 1998) in people's age and dull-witted stage.The brain glucose metabolism speed that dog also shows the part relevant with the age reduces (London
People such as ED, 1983).Dog shows dependent variation of age (people such as Tapp PD, 2005 and Su MY, 1998) aspect LCBV and blood-brain barrier permeability (it may be relevant with the change of brain structure and neuropathology).
Shown that before medium chain triglyceride (MCTs) can be used for strengthening or keeping the cognitive function of elderly population.MCTs is made up of the fatty acid chain that becomes ester with glycerol backbone.The ketoboidies that is obtained by MCTs can provide as the energy of selecting with the energy deficiency of the neuronal cell that replenishes patients with Alzheimer disease (people such as Reger MA, 2004, U.S. Patent number 6,323,237 and 6,316,038).When the part as long-term nourishment maintenance scheme was applied, MCTs also showed some cognitive skill (WO 2007/070701) that can keep or improve old and feeble dog.
Although obtained progress, but need to improve cognitive composition and method, particularly in the people and other animals of aging.Also need to be used for the treatment of and/or to prevent the composition and the method for Cognitive function damage.Described treatment can be used for improving the whole quality of life that all relate to animal.For companion animals, these treatments can improve owner's satisfaction, and the relation of promoting owner and companion animals.
Summary of the invention
Therefore, an object of the present invention is to provide composition and the method that is used to strengthen the animal cognitive function.
Another object of the present invention provides in animal and to reduce or prevention social interaction decline, minimizing or the prevention behavior relevant with the age change, increase trainability, keep best cerebral function, promote learning and memory, reduce the memory loss, delay aging of brain, the method for prevention or treatment apoplexy and prevention or treatment dementia.
Further purpose of the present invention provides the product with cover box-like formula, and described cover box comprises one or more food or other compositions and devices of can be used for producing the compound of the present composition and can be used for strengthening the animal cognitive function.
Another object of the present invention provides the packing that comprises the present composition and invest the label on the packing, and described label is indicated the content of this packing and/or this composition is applied to the benefit of animal.
Use is used to strengthen the new composition of cognitive function and method and has realized one or more these other purposes.Usually, described composition comprises one or more long-chain polyunsaturated fatty acids, nitric oxide release property compound and medium chain triglyceride.Described method generally includes to animal and uses the composition that is used to strengthen the animal cognitive function, particularly prevent, reduce and/or delay the effective dose that the cognition relevant with the age descend,
Those skilled in the art find out other and further purpose, feature and advantage of the present invention easily.
Detailed Description Of The Invention
Definition
Following abbreviation can be used for this paper: MCTs, medium chain triglyceride; AA, arachidonic acid; ALA, alpha-linolenic acid; ANOVA, variance analysis; DHA, DHA; DPA, clupanodonic acid; EPA, eicosapentaenoic acid; LA, linoleic acid; LCPUFA, long-chain polyunsaturated fatty acid (LCPUFA that is used for this paper refers to one or more described fatty acid); NO, nitric oxide; NORC, nitric oxide release property compound; And L-Arg, the L-arginine.
Term " animal " is meant any animal that can benefit from one or more methods of the present invention, it comprises the enhancing cognitive function; Change cognition, motion or ethological function; Reduce or prevention social interaction reduction; Minimizing or the prevention behavior relevant with the age changes; Increase trainability; Keep optimum cerebral function; Promote learning and memory; And/or reduce and remember loss.Usually, described animal is people, birds (avian), bovine (bovine), canid (canine), horse class animal (equine), cats (feline), goat class animal (hicrine), wolf class animal (lupine), murine (murine), sheep class animal (ovine) and porcine animals (porcine).Preferably, term " animal " is meant the animal that the animal of needs enhancing cognitive function maybe can benefit from the improvement of cognitive function." companion animals " is any domestic animal, and comprises cat, dog, rabbit, cavy, ferret, hamster, mouse, gerbil jird, horse, milk cow, goat, sheep, donkey, pig etc. without limitation.Preferably, animal is people or companion animals such as dog or cat.
Term " enhancing cognitive function " is meant in animal increases cognitive, motion or behavioral function or prevention, reduces or delays in the reduction of cognition, motion or behavioral function one or more.
" medium chain triglyceride " or " MCTs " is meant any glycerol molecule that is connected by ester bond with three fatty acid molecules, and wherein each fatty acid molecule contains 5-12 carbon atom.MCTs can be represented by following general formula (formula 1):
Figure GPA00001087146900051
Wherein R ', R " and R " ' be with the carbon skeleton of glycerol backbone esterification in contain the fatty acid of 5-12 carbon atom.Lipid of the present invention can prepare by any method known in the art, as direct esterification, rearrangement reaction, fractionation, ester exchange reaction etc.For example, this lipid can prepare by the rearrangement reaction of vegetable oil such as cocoa butter.The length of this chain length and distribution can change according to the source of oil.The MCTs that for example comprises 1-10%C6,30-60%C8,30-60%C10,1-10%C10 derives from palm oil and cocoa butter usually.R ', R " and R " ' on comprise the MCTs that surpasses about 95% C8 and can prepare with semi-synthetic esterification glycerine by sad.Can use the mixture of the MCTs that comprises about 50% total C8 and/or about 50% total C10 in this article.Above-mentioned MCT composition be obtained commercially and be well known by persons skilled in the art.These MCTs effects are similar, and are encompassed among the term MCTs used herein.
Term " long-chain polyunsaturated fatty acid " or " LCPUFA " are meant any or multiple monocarboxylic acid with at least 20 carbon atoms and at least two two keys.The example of LCPUFA comprises (n-6) fatty acid such as arachidonic acid (AA) and (n-3) fatty acid such as eicosapentaenoic acid (EPA), clupanodonic acid (DPA) and DHA (DHA).
Term " fish oil " is meant the fat that is rich in LCPUFA relatively or the oil extract of crude product or pure product, it is from marine animal, be preferably cold water fish as (but being not limited to) salmon, tuna, mackerel, catfish, orange rock-fiss, Tiao Wen Shi Sushi, halibut, catfish and sardine, and shark, shrimp and clam, or its combination.Fish oil is the term in the employed field of material supplier normally, and comprises the different PUFA compositions and the scope or the product of purity.
Term " nitric oxide release property compound " or " NORC " are meant and cause any compound that maybe can cause nitric oxide production release in animals.Described examples for compounds comprises the L-arginine; contain arginic peptide class of L-or protein; and known or definite nitric oxide production analog or derivative of discharging; as the arginine α-Tong Wuersuan; GEA 3175; sodium nitroprussiate; monobel; S-nitroso-N-acetyl group-penicillamine; nitroglycerin; the S-NO-glutathione; the nonsteroidal anti-inflammatory agent that NO-puts together (for example; the NO-naproxen; the NO-aspirin; the NO-brufen; the NO-Diclofenac; NO-Flurbiprofen and NO-Ketoprofen); NO-release property compound-7; NO-release property compound-5; NO-release property compound-12; NO-release property compound-18; diazeniumdiolate class (diazenium diolates) and derivative thereof; diethylamine NO-nucleophilic complex (NONOate), and in animal, cause nitric oxide; any organic or inorganic compound that the NO that particularly " dissociates " discharges; biomolecule or its analog; homologue; conjugate or derivative.
" effective dose " is meant compound, material, composition, medicine or other amount of substances, and it can reach specific biological effect effectively.These effects include but not limited to one or more following effects: strengthen cognitive function, increase the activity on daytime, improve study (speed of study and easiness), improve notice, improve social action, improve locomitivity and/or improve cerebrovascular function, particularly for the animal of aging.In various embodiments, " effective dose " is meant the amount that is suitable for preventing the reduction of any one or more in the above-mentioned characteristic, or in certain embodiments, be meant and improve any or multiple amount in the above-mentioned characteristic, described characteristic is cognitive function or behavior, pace of learning or ability, ability to solve problem, the scope of notice and ability, motor function or the behavior and the social action etc. of concern task or problem for example.In other embodiment, effective dose is suitable for reducing the degree or the speed of the decline of animal cognitive skill or function, and/or effective dose is suitable for delaying the beginning of this type of reduction.Described effect can be for example realizes by animal or animal population are used composition of the present invention.Preferably, the prevention of described decline, reduce or delay, or the improvement of individuality or colony is with respect to group's same period (cohort), for example also accept the control-animal disposed or the same period colony, used composition or medicine the contrast control-animal or the same period colony.
Term " cognitive function " is meant specific, the normal or suitable physiologically active of brain, and it comprises one or more following physiologically actives: mental toughness, memory/memory ability, ability to solve problem, inferential capability, elaborative faculty, judgement, identification or deciding ability, learning ability, ease of learning, perception, intuition, notice and consciousness." recognizing ability of enhancing " or " recognizing ability of improvement " is meant any improvement of specific, the normal or suitable physiologically active of brain, and it comprises the following physiologically active that one or more are measured by any suitable method in this area: mental toughness, memory/memory ability, ability to solve problem, inferential capability, elaborative faculty, judgement, identification or deciding ability, learning ability, ease of learning, perception, intuition, notice and consciousness.
Term " behavior " is meant that animal is owing to the response of the environment of given stimulation or setting or anything that reaction is made." behavior of enhancing " or " behavior of improvement " is meant that animal is owing to the response of the environment of given stimulation or setting or reaction is made any improvement of anything." behavior " and " behavioral function " synonym herein.
" motor function " or " motor behavior " is meant influence or causes the biologically active of the tissue of animal movement.This class tissue includes but not limited to muscle and motor neuron." motor behavior of enhancing (or function) " or " motor behavior of improvement (or function) " is meant influence or causes bioactive any improvement of the tissue of animal movement.
In individual (phenotype) characteristic of any mentioned kind or particular type or function in term " decline " typically refer to the improvement of this characteristic or function or strengthen opposite." effective dose " of composition can be to prevent fully to descend or prevention decline in fact (" prevention " descends), reduce when phase in office or the degree that descends at any time or speed (" minimizings " descends), the needed amount of the generation that delays to descend, degree or progress (" delaying " decline).When being used for not ill aged animal (for example, " healthy aged animal "), the prevention of " declines ", reduce or to delay normally more effective contrast basic.Can think prevention, reduce or delay be with respect to the contrast of not accepting disposal (for example interested diet or replenishers) or the same period group.Can be on the individual primary or in certain embodiments on the colony basis, measure and consider prevention, reduce or speed that the characteristic that delays to be harmful to or illness outbreak or specific function descend.The net effect of preventing, reducing or delay to descend is in time per unit or the less decline of cognition when given terminal point, motion or behavioral function.In other words, for individuality or colony, it is desirable on the highest possible level, keep understanding, motion and behavioral function to reach the longest possible time.Thereby for any embodiment, cognition, motion or behavioral function do not need net increase.For the purpose of this paper, can compare with contrast individuality, group or colony individual.Equally can be with colony with actual individual relatively so that to the bioassay standardization of individuality, or with group or colony relatively, it also is useful.
Term " old and feeble " is meant advanced age, described animal surpassed the kind in its specific species and/or the species the average life cycle 50%.For example, if the average life cycle of the dog of certain given kind is 10 years, 5 years old the dog of surpassing for this kind of this paper purpose is considered to " aging " so." healthy aged animal " be do not have known disease, particularly not with the animal of the cognition forfeiture infringement diseases associated that may obscure effect.Use healthy aged animal under study for action, the same period group the also preferred healthy aged animal of animal, though have the sample that other healthy animal of suitable cognition, motion or behavioral function can be suitable for use as comparison.If use the animal have the specified disease diagnosis or to have cognition, motion or behavioral deficiency, so described same period group should comprise animal with similar diagnosis have the indication of similar and described disease or cognition, motion or behavioral deficiency animal.
Term " food " or " food product " or " food compositions " are meant product or the composition that is used for also being provided for it subsequently by animal (comprising the people) picked-up nutrition.
This paper employed " consuming made food for human " is any composition that clearly is intended to be used for by people's picked-up.Term " pet food " or " pet food composition " are meant the composition that is intended to by animal, preferred companion animals consumption.The pet food of nutrient balance " fully and " be with suitable amount and ratio comprise all known for food the expection recipient or the food of the required nutrient of consumer, described nutrient is based on authority's recommendation of for example generally acknowledging in the field of companion animals nutrition.Thereby this based food can earn a bare living or promote and produce as the single source of picked-up diet, and do not add the source of nutrition of complementarity.The pet food composition of nutrient balance is well-known and uses in the art.This term comprises any food, feed, dessert, dietary supplement ingredient, snacks (treat), generation meal or dietary substitute, no matter is that human or another kind of animal are used.Animal foodstuff comprises that expection is used for any domestic or food or feed that wildlife is used.In preferred embodiments, animal foodstuff is represented the wholefood composition, for example the ball shape, extrude or dried foods.The example of this class animal foodstuff comprises the pet food of extruding, for example dog food and cat food.
Term " diet supplement " is intended to be used for the product that absorbs except that the intact animal diet.Diet supplement can be any form, for example solid, liquid, gel, tablet, capsule, pulvis etc.Preferred they provide with formulation easily.In some embodiments, they provide with marketing packing in bulk such as bulk powder, liquid, gel or grease.In other embodiments, replenishers provide with amount in bulk, and it is contained in other food products, as dessert, snacks, additional rod, beverage etc.
Term " chronic administration " is meant the period of using repeatedly or consuming more than one month.For some embodiment preferred 2 months, 3 months or the period more than 4 months.In the also preferred period that more prolongs, comprise 5,6,7,8,9 or the period more than 10 months.Also preferred period more than 11 months or 1 year.This paper also comprise extend to 1 year, 2 years, more than 3 years or more long-term application more for many years.Under the situation of some aged animal, this animal is pressed the described composition of the lasting consumption of application program clocklike in its remaining life.
" application program clocklike " used herein be meant at least every month once, more preferably weekly administration or consume described composition.Preferably administration or consumption more continually in certain embodiments is as twice or three times weekly.Also more preferably comprise the scheme that consumes every day at least once.It will be appreciated by those skilled in the art that the concentration of some metabolite in blood that produces after some metabolite of compound or this compound or this compound consumption can be to estimate or measure the useful instrument of administration frequency.For example, contain the dosage or the dose frequency of the composition of MCTs for mensuration, the haemoconcentration of ketoboidies class or specific ketoboidies can provide Useful Information.No matter whether carried out illustration clearly in this article, the administration frequency that the expection haemoconcentration of the compound of being surveyed is remained in the tolerance interval can be considered to effective in this article.It will be appreciated by those skilled in the art that administration frequency is to be consumed or by the function of the composition of administration, some compositions is used with may needing higher or lower frequency, is surveyed the blood levels of compound (for example ketoboidies) expection to keep.
Term " Orally administered " or " dosage forms for oral administration " are meant animal picked-up one or more compositions as herein described or the people feeds or one or more compositions as herein described of feeding are under guidance given animal.People's said composition of feeding under guidance wherein, this guidance can be introduction and/or inform that people use said composition can and/or will provide the benefit of mentioning, for example strengthen cognitive function, improve liver function, increase the activity on daytime, improve study, improve notice, improve social action, improve locomitivity and/or improve cerebrovascular function, or reduce, prevent or delay the decline of above-mentioned functions or characteristic.This guidance can be that oral guidance (for example comes doctor freely, animal doctor or other healthy professional persons' verbal communication), or broadcasting or TV media (for example advertisement), or written guidance (is for example come doctor freely, the guidance that animal doctor or other healthy professional persons (as the prescriber) are write), specialty sellers or tissue (for example pass through as market propaganda handbook, brochure or other guiding apparatus), written medium (internet for example, Email, website or other medium relevant with calculator) and/or the related packaging of composition (label on the container of said composition for example is housed), or its combination (for example, having label or the package insert of access websites) with the explanation of obtaining more information.
Term " cognitive medicine " is meant any compound, composition or the medicine that is used to influence cognitive function, for example monoamine oxidase B inhibitors such as selegiline; Vasodilator such as Nicergoline and vinpocetine; Phosphatidylserine; Propentofylline; Anticholinesterase (anticholinesterase) as Tacrine, galanthamine, thunder department for bright, vinpocetine, donepezil (ARICEPT
Figure GPA00001087146900101
(donepezil hydrochloride)), Bilarcil and eserine; Lecithin; Choline cholinomimetic such as Milameline and xanomeline; Ionic N-methyl-D-aspartate (NMDA) receptor antagonist such as Memantine; Antiinflammatory agent such as prednisolone, Diclofenac, Indomethacin, Propentofylline, naproxen, rofecoxib, brufen and sulindac; Metal chelating agent such as chinoform; Ginkgo (Ginkgo biloba); Bisphosphonates (bisphosophonate); Selective estrogen receptor modulators such as Raloxifene and oestrogenic hormone; β and γ and Secretase inhibitors; Gemfibrozil such as statins; Calcitonin; Risedronate; Alendronate; And their combination.
Term " associating " be meant with identical or different frequency, use identical or different route of administration, ask to join one the time or periodically with composition (it comprises LCPUFA, NORC and MCTs), food compositions, cognitive medicine or the present invention other compound composition (1) together in food compositions or (2) be administered to animal respectively." periodically " be meant so that the acceptable administration schedules of particular active agent is used described activating agent, and with the mode that is fit to specific animal with food routinely feeding give animal." ask to join one the time " and generally be meant food or activating agent in the identical time or in about 72 hours, use each other." associating " especially comprises following application program: wherein cognitive medicine is used during predetermined and the composition that contains LCPUFA, NORC and MCTs is used indefinitely.
Term when relating to animal " independent " is meant the independent animal of any species or kind.
Term " microorganism " comprises bacterium, mould and other fungies and saccharomycete at least.Probio be can in the intestines and stomach of animal, survive or even breeding and vigorous useful microorganism, probio can help the health of the integral body of animal usually, and helps the health of the stomach and intestine of animal especially.
The component that term " individual packaging " means the cover box is associated physically, and described component is in one or more containers or use one or more containers, and it is considered to the unit that makes, distribute, sell or use.Container includes but not limited to, the packing of box or carton box, bottle, any kind or design or material, external packing, shrink wrapping, component (for example, stitching, bonding etc.) or any aforesaid combination of adhering to.For example, individual packaging cover box can provide physically relevant each the independent composition and/or the container of food compositions, thereby they are considered to the unit that makes, distribute, sell or use.
Term " virtual package " is that the component of fingerstall box is associated by the specification that how to obtain other components to user explanation on one or more cover box components physically or virtual, for example, in the bag that contains a component and guidance or other containers, described guidance is gone the information of website, relationship record or is replied fax services, browses visual information or contact caregiver or director with the specification that obtains how to use this cover box or about the safety or the technical information of one or more components of overlapping box to user explanation.Can be as the part of virtual cover box and the information that provides comprises operation instructions; Security information such as MSD Sheets; Poison control information; Potential bad reaction information; The clinical research result; Meals information such as food are formed or heat is formed; General information about cognition, behavior or motor function; The disease of influence cognition, behavior or motor function; Treatment cognition, behavior or motor function; Or about treating or prevent the general information of cognition, behavior or motor function; Self-service about cognitive, behavior or motor function; Be used to nurse the caregiver's of the animal that suffers cognition, behavior or motor function infringement information; Use, benefit and potential side effect or contraindication with cognitive medicine.
Unless otherwise specified, all percentages as herein described are the percentage by weight that accounts for based on the composition of dry matter.Those skilled in the art will appreciate that term " based on dry matter " is meant that any free moisture is removed concentration or the percentage that the composition in the composition was measured or measured in the back in composition.
As in full employed, use each scope with the form of writing a Chinese character in simplified form, so that avoid at length launching and describe each numerical value in the described scope.When suitable, can be chosen in any suitable numerical value in the described scope as the high value of scope, than the end value of low value or scope.
Unless point out clearly in addition in the context, otherwise the singulative of employed word comprises plural number in this paper and claims that vice versa.Thereby, when mentioning odd number, generally include the plural number of corresponding term.Also comprise its plural form when for example mentioning the singulative of " pup " " method " or " food ".Comprise the plural form of this antioxidant during the singulative of for example " antioxidant " that this paper mentions, and comprise single part when mentioning " each several part ".Similarly, wording " comprises " and " containing " will be interpreted as being included in interior rather than exclusive.Similarly, term " comprise " and " or " should be interpreted as being included, unless clearly forbid such explanation herein.Use term " example " part in this article, particularly when it is positioned at after one group of term, described " example " only is exemplary with illustrative, and should not be considered to monopolistic or popularity.
Method and composition disclosed herein and other progress are not limited to maneuver described herein, scheme and reagent, and reason is as understood by one of ordinary skill in the art, and these contents can change.In addition, wording used herein or term only are for describing the purpose of particular, and unrestricted and the plan restriction is disclosed or the scope that requires.
Unless otherwise defined, whole technology used herein and scientific terminology, field term and acronym have the implication with the those of ordinary skill common sense in field of the present invention or the employed field of described term.Although in enforcement of the present invention, can use and those similar or suitable any compositions as herein described, method, product or other means or material, describe preferred compositions, method, product or other means or material herein.
This paper is quoted or the full content of whole patents, patent application, publication, technology and/or the scholar's paper mentioned and other list of references is introduced this for as a reference with allowed by law degree.These lists of references are discussed only be intended to summarize wherein opinion.Do not admit that any described patent, patent application, publication or list of references or its any part are the material or the prior arts of being correlated with.The special reservation, queried the accuracy of any opinion that described patent, patent application, publication and other list of references are relevant material or prior art and the right of appropriateness.
Invention
On the one hand, the invention provides the composition that is applicable to enhancing animal cognitive function.Described composition comprises one or more long-chain polyunsaturated fatty acids (LCPUFA), one or more medium chain triglycerides (MCTs) and one or more nitric oxide release property compounds (NORC) of the amount of effective enhancing animal cognitive function.In certain embodiments, described composition also comprises one or more vitamin B group, one or more antioxidants or its combination.The present invention is based on following discovery: the composition that comprise LCPUFA, NORC and MCTs, is with or without vitamin B group and/or antioxidant is effective to strengthening the animal cognitive function.Described composition is used for influencing one or more cognitions, motion or behavioral function animal, no matter and health of animal or age how, for example childhood, grow up or old animal.Described composition increases one or more cognitions, motion or behavioral function in animal, described animal comprises the healthy animal of institute's has age or easily suffers from or suffer from the animal of the cognitive function decline that is caused by ageing process or disease.Similarly, composition prevents, will less or delay the animal cognitive function and descends, and particularly easily suffers from or suffer from the animal of the aging of the cognitive function decline that is caused by ageing process or disease.Described composition in people and companion animals (particularly dog and cat) to reducing or to delay effect relevant with the age or the relevant cognitive decline of disease effective especially.When cognition descend be by cerebral function change, aging of brain or by disease when particularly the damage that causes of apoplexy is caused, described composition also is used to strengthen cognitive function particularly.
LCPUFA can be any LCPUFA that is fit to be administered to animal.LCPUFA can derive from any suitable source, can be synthesize or natural sources.It is the natural origin of described fatty acid that LCPUFA preferably originates, and comprises primula, bottle green vegetables such as spinach without limitation; Algae and blue-green algae such as Spirullina plant (spirulina); Plant seed and plant oil are as flax, canola, soybean, English walnut, custard squash, safflower, sesame, wheat, sunflower, corn and hemp; With fish such as salmon, tuna, mackerel, catfish, orange rock-fiss, Tiao Wen Shi Sushi, halibut, catfish, sardine, shark, shrimp and clam; With above-mentioned any or multiple extraction oil.LCPUFA also synthesizes, and itself can be according to any suitable method in this area by any suitable feedstock production.LCPUFA should be understood and mixture can be comprised from any or multiple LCPUFA in any or multiple source (the natural or synthetic source of those that exemplify as mentioned).
MCTs can be any MCT that is fit to be administered to animal.MCTs can derive from any suitable source, can derive from synthetic or natural sources.The example of the MCT of natural origin comprises plant origin such as coconut and cocoa butter, palm kernel and palm-kernel oil, and animal origin is as the milk from any species in the multiple species.In certain embodiments, LCPUFA comprises one or more (n-3) fatty acid such as ALA, EPA, DPA and DHA.NORC comprises one or more L-Arg and nitric oxide release property derivative thereof in certain embodiments.In preferred embodiments, MCT comprises the compound with formula 1 structure, and wherein esterification is in R ', the R of glycerol backbone " and R " ' each has the independently fatty acid of 5-12 carbon naturally.In certain embodiments, surpass about 95% R ', R " and R " ' length be 8 carbon.Remaining in some embodiments R ', R " and R " ' are the fatty acid of 6-carbon or 10-carbon.In other embodiment, surpass at least or about R ' of 30,40 or 50%, R " and R " ' they are C8, and/or above at least or about R ' of 30,40 or 50%, R " and R " ' be C10.In one embodiment, about 50% R ', R " and R " ' be C8, and about 50% R ', R " and R " ' be C10.
NORCs can be any NORC that is fit to be administered to animal.NORCs can derive from any suitable source, can derive from synthetic or natural sources.In multiple embodiments, NORC comprises arginine.Arginine is preferably originated and is comprised animal and plant albumen without limitation at present.The example that is considered to the plant of being rich in arginine and being applicable to this paper comprises beans such as soybean, lupine and angle beans without limitation; Cereal such as wheat and rice and fruit such as grape.The seed of plant such as cocoa and peanut and nut also are considered to be rich in arginine, and therefore can be used for this paper.Some examples that are considered to be rich in arginic suitable animal protein are poultry and fishery-ies product.NORC can also be according to the synthetic preparation of any suitable method of this area.The same with LCPUFA, the NORC of any composition disclosed herein can comprise the mixture of any natural or synthetic NORC.No matter it is natural or synthetic for LCPUFA and NORC, can both directly obtain or provides by being purchased approach.
On the one hand, described composition further comprises one or more vitamin B group, one or more antioxidants or its combination.Vitamin B group can be any vitamin B group that is suitable for being administered to animal.Vitamin B group comprises that vitamin B1 (thiamine), B2 (vitamin b3), B3 (also claiming P or PP) (niacin comprises nicotinic acid and/or vitamin PP), B5 (pantothenic acid), B6 (pyridoxine), B7 (also claiming H) (vitamin h), B8 (inositol), B9 (also claiming M or B-c) (folic acid), B12 (cobalamin) or its are considered to find to have salt, conjugate or the derivative of vitamin B group activity.Aforementioned any one combination also can be used for this paper, and is called as " mixture " of vitamin B group in this article sometimes.Because to need changing of vitamin, so the not all compound of listing all is considered to vitamin to all species with species are different.For example, because known person can be synthesized inositol, thus do not think that it is a vitamin, because it is unwanted for sufficient human nutrition.Antioxidant can be any antioxidant that is suitable for being administered to animal.Antioxidant is known in this area, particularly food technology and food preparation field.The natural anti-oxidation immunomodulator compounds comprises vitamin (as A, C and E and derivative, conjugate or analog), and plant extracts, and it comprises the extract from other types of fruit, vegetables, Chinese herbal medicine, seed and plant and/or part.Known compound such as alpha-lipoic acid, chlorophyll and derivative thereof, glutathione, panthenol class (for example Co-Q10), carotenoids (for example, lycopene), flavonoids, phenolic acid and polyphenol and pycnogenol (pyenogenol) are extraordinary antioxidants.Some embodiment of the antioxidant of plant origin comprise from those of fruit such as berry (cherry, blackberry, blueberry, strawberry, raspberry, red crowberry (crowberry), blueberry, whortle/wild blueberry, black-currant), pomegranate, glucose, orange, plum, pineapple, kiwi fruit and grapefruit; Comprise those of kale, capsicum, red cabbage, pepper, caraway, artichoke, brussels sprouts, spinach, lemon, ginger, garlic and red beet from vegetables; From those of dry fruit such as apricot, prune and nipa palm; Comprise those of broad bean, pinto (pinto bean) and soybean from beans.Also have nut and seed such as pecan, walnut, fibert, peanut and sunflower seeds; Cereal such as barley, grain, oat and corn.Many natural antioxidants also can be from obtaining the species very widely, and it comprises cloves, Chinese cassia tree, rosemary, and wild marjoram (oregano).The antioxidant source of not too extensively understanding comprises ginkgo and tropical plants such as uyaku and papaya papaw.The antioxidant properties of various tea and green tea and fermented product such as claret has caused very big interest in recent years, and can be suitable for use in this paper.Selenium is splendid oxygen scavenger, and especially with vitamin or relevant tocopherols compound one time-out exhibits excellent.Synthetic meals antioxidant comprises butylated hydroxyanisol (BHA) and Butylated Hydroxytoluene (BHT), and it is generally used in the food product.Any above-mentioned every form with alone or in combination is suitable for this paper, and the combination of natural and synthetic antioxidant also is like this.
Described composition comprises LCPUFA, NORC and the MCTs of the amount of effective enhancing cognitive function, if reach vitamin B group and antioxidant when being included in the composition.Usually, described composition comprises about 0.1% to about 50%LCPUFA, about 0.1% to about 20%NORC and about 1% to about 30%MCTs.In the time of in being included in composition, described composition comprises the vitamin B group of about 0.1 to 40 times recommendation daily requirement (RDA) and the antioxidant of about 0.1 to 25 times RDA.In multiple embodiments, composition comprises about 1 to about 30%LCPUFA, and preferred about 1 to about 15%LCPUFA; About 1 to about 15%NORC, and preferred about 1 to about 10%NORC; With about 1% to about 20%MCTs, preferred about 1 to about 12%MCTs, most preferably from about 1 to about 8%MCTs.In multiple embodiments, vitamin B group comprises about 1 to 20 times RDA, and preferably about 1 to 10 times RDA, and antioxidant comprises about 0.01 to 15 times RDA, more preferably from about 0.01 to 5 times RDA, most preferably from about 0.01 to 2 times RDA.In one embodiment, composition comprises LCPUFA, NORC and the MCTs of described amount, and the mixture of one or more vitamin B group and one or more antioxidants.In one embodiment, composition comprises about 10g to about 30gMCT, about 0.5g about 10g LCPUFA and about 0.5g about 10g NORC extremely extremely, and it comprises or do not comprise vitamin B group and the antioxidant of RDA.
Described composition can further comprise material such as mineral matter, other vitamins, salt, functional additive, and described additive comprises for example palatant, colouring agent, emulsifier, antibacterial agent or other preservatives.The mineral matter that can be used for described composition comprises, for example calcium, phosphorus, potassium, sodium, iron, chlorine, boron, copper, zinc, magnesium, manganese, iodine, selenium etc.The example that is used for the additional vitamins of this paper comprises fat-soluble vitamin such as vitamin A, D, E and K.Inulin, amino acid, enzyme, coenzyme etc. can be used for being included in the multiple embodiments.
In one embodiment, composition is a food compositions, and it comprises people's food compositions, pet food composition.Such composition comprises and aims to provide the essential dietetically desirable food of animal, animal snacks (for example, biscuit) or diet supplement.Said composition can be the composition of doing (for example, coarse grain food (kibble)), the composition that partly wets, wet composition or its any mixture.In another embodiment, said composition is a diet supplement, for example meat soup, drinking water, beverage, yogurt, powder, particle, paste, suspension, chaw, mince (morsel), snacks, dessert, micro chip (pellet), pill, capsule, tablet or any form that other is fit to send.Diet supplement can comprise LCPUFA, NORC and the MCTs and the optional vitamin B group and the antioxidant of high concentration.This makes this fill-in to be applied to animal with a small amount of, perhaps, and can be diluted before using to animal.Diet supplement may need with water or other mixing diluents before animal is used or preferably mix with it.
In one embodiment, composition is refrigeration or freezing composition.In another embodiment, LCPUFA, NORC and MCTs and other component premixed are to provide required useful amount.In another embodiment, LCPUFA, NORC and MCTs are used for bag by food, dessert, pet food composition or pet treat.In one embodiment, LCPUFA, NORC and MCTs are added composition before offering animal facing, for example use and spray powder or mixture.Described composition can further comprise vitamin B group and/or antioxidant.
Composition can randomly comprise one or more promotions or keep the material that replenishes of general health.The mental health of preferred material and improvement or the cognitive function of enhancing are relevant, maybe can be inhibition, delay or reduce the material that cognitive function loses, the Chinese herbal medicine or the plant that for example can strengthen cognitive function.
In multiple embodiments, pet food or pet treat composition comprise about 15% to about 50% thick protein.Described thick protein material can comprise vegetable protein such as soybean meal, soy protein concentrate, maize gluten powder, wheat gluten, cottonseed and peanut powder, or animal protein, as casein, albumin and meat albumen.The example that can be used for the meat albumen of this paper comprises pork, lamb meat, horse, poultry, fish and composition thereof.
Described composition can further comprise about 5% to about 40% fat.Described composition also can comprise carbohydrate source.Described composition comprises about 15% to about 60% carbohydrate.These examples of carbohydrates comprise cereal or grain, as rice, corn, chinese sorghum, jowar, clover, barley, soybean, canola, oat, wheat and composition thereof.Said composition also can randomly comprise other materials, as doing whey and other dairy by-products.
In some embodiments, composition content of ashes scope is at least 1% to about 15%, preferred about 5% to about 10%.
Water content can be according to the change of properties of composition.In preferred embodiments, composition be completely with the pet food of nutrient balance.In this embodiment, pet food can be " wet provision ", " dry food " or the medium food of water content." wet provision " describes the pet food of selling usually in jar or paper tinsel bag, and has common water content in scope about 70% to about 90%." dry food " describes the pet food that has similar composition with wet provision, but contains the water content of finite quantity, usually in about 5% to about 15% or 20% scope, and therefore as the coarse material existence of for example little Biscuits.In a present embodiment preferred, composition has about 5% to about 20% water content.The dried foodstuff product comprises the multiple food with multiple water content, so its normal temperature is relatively stable, and antimicrobial or fungi is rotten or pollute.Also preferred dry food composition, it is the food product of extruding, as the cakes of pet food or people or companion animals.
Composition also can comprise at least a fibre source.Term " fiber " comprises " fibrous substance " in all sources in the food, and no matter it is digestiblely or indigestible, soluble or insoluble, fermentable maybe can not ferment.Preferred fiber is originated as thalassophyte from vegetalitas, but also can use microbe-derived fiber.Can utilize multiple solvable or insoluble fiber, they will be for known to those of ordinary skills.Fibre source can be sugar beet pulp (from beet), gum Arabic, tal fibre Kazakhstan natural gum (gum talha), psyllium, rice bran, carob, citrus pulp, pectin, fructo-oligosaccharide (FOS), the few fructose of short chain, the few fructose (mannanoligofructose) of mannan, fibre and soya, arabinogalactan, galactooligosaccharide, arabinose sill glycan or its mixture.
Perhaps, fibre source can be fermentable fiber.It is useful to the immune system of companion animals before to have described fermentable fiber.Fermentable fiber or well known to a person skilled in the art provides prebiotics also can be impregnated in composition of the present invention with other composition that strengthens probiotic microorganisms growth in the intestines to strengthen by the benefit to animal immune system provided by the invention helping.
In other embodiment, composition further comprises prebiotics or probio.Probio is ingested the back for preventing and treat the microorganism that specific medical condition has the work of useful effect.It is believed that the phenomenon performance biological effect of the resistance (colonization resistance) of probio by being called field planting.For the process of the concentration of potential harmful (mainly being aerobic) bacterium in the indigenous anaerobic bacteria flora restriction digestive tract in the digestive tract, probio has facilitation.Other binding mode also can illustrate some other functions owing to probio as enzyme being provided or influencing enzymic activity in the digestive tract.Prebiotics is indigestible composition of food, its growth by the bacterium in the selective stimulating colon and/or active and host health is produced favourable influence.Prebiotics comprises fructo-oligosaccharide (FOS) (FOS), xylo-oligosaccharide (XOS), galactooligosaccharide (GOS) and Oligomeric manna sugar (being generally used for non-human food such as pet food).Prebiotics---fructo-oligosaccharide (FOS) (FOS) is found natural and is present in the multiple food as wheat, onion, banana, honey, garlic and leek.FOS can also separate from cichory root, or synthetic through enzyme process by sucrose.The fermentation of FOS in colon can produce many physiological actions, and it comprises the quantity that increases the Bifidobacterium in the colon, increases calcium absorption, increases stool weight, shortens the stomach and intestine transmission time, also may reduce blood lipid level.The increase of Bifidobacterium is by the compound that produces the inhibition potential pathogen, by reducing the blood ammonia level and being of value to health by producing vitamin and digestive ferment by inference.Probio such as Bacillus acidi lactici or Bifidobacterium it is believed that it is by the improvement intestinal microbial balance, thereby cause production of antibodies to increase and leukocytic engulfing (conquer and annex or kill) increased activity, come the positive influences immune response.Bifidobacterium lactis (Bifidobacterium lactis) may be the profitable living diet supplement that strengthens the cellular immunity of some aspect of the elderly.Probio can strengthen the systemic cell immune response, can be used as diet supplement and promotes the healthy in other respects adult innate immunity.Probio comprises the bacterium of many types, but is selected from the bacterium of following four genus usually: lactobacillus acidophilus (Lactobacillusacidophilus), Bifidobacterium (Bifidobacteria), lactococcus (Lactococcus) and Pediococcus (Pediococcus).Useful bacterial classification comprises enterococcus spp (Enterococcus) and Blastocystis (Saccharomyces) bacterial classification.To be administered in the probio of animal and the amount of prebiotics, by the technical staff according to the type of probio and prebiotics and type and the characteristic of characteristic and animal, for example the existence and the meals of the degree of the age of animal, body weight, general health situation, sex, microorganism loss, noxious bacteria are determined.Usually, keep health in order to make intestinal microflora, the quantity that is applied to the probio of animal be about 1,000,000,000 to about 20,000,000,000 colony-forming units (CFU)/sky, preferred about 5,000,000,000 to the about 10,000,000,000 bacterium/skies of living.Usually, prebiotics is used with the amount that is enough to the healthy micropopulation in the positive sexual stimulus enteron aisle, impels these " good " bacterial reproductions.Common amount of application is every portion of food about 1 to about 10 grams, perhaps accounts for animal and recommends about 5% to about 40% of dietary fiber every day.Probio and prebiotics can be made the part of composition by any suitable means.Usually, they are mixed with composition, perhaps be applied to the surface of composition, for example undertaken by spreading or spraying.When they be the cover box a part of the time, these materials can with other material fusion, perhaps be in themselves the packing.
Recipient or consumer that composition and diet supplement can be expection prepare especially, as are adults or older or young animal preparation.The composition that for example, can prepare composition that is fit to doggie or kitten or animal that be fit to enliven, conceived, lactation or old and feeble.In a word, specific composition can comprise the energy and the nutrition of the animal needs that are fit to be in different growing stage or age.
Some aspect of the present invention is preferred and uses with the combinations of foods of balance completely.According to some embodiment provided herein, the composition that comprises LCPUFA, NORC and MCTs preferably uses with high-quality commercialization food.As used herein, " high-quality commercialization food " refers to be prepared as the digestibility that main nutrients is provided and reaches 80% or higher diet, for example in the recommendation of the above-mentioned international research committee to the dog class, or in the guilding principle that proposes by U.S. food control official association (AssociationofAmerican Feed Control Officials), proposed.For other animals, use similar high trophic level.
In one embodiment, food compositions comprises the multiple composition the contribution of total composition selected according to them or any material in its combination.Therefore, skilled food technology personnel can select from natural (for example plant or plant derivation, animal or animal derived and microorganism or microorganism derive) and synthetic ingredient or component.In specific embodiment, these compositions can comprise egg, vitamin, mineral matter, salt, sweetener, fiber, flavouring or palatant, colouring agent and the functional components in any cereal and part or component, meat and meat accessory substance, fish, shellfish or other marine products, other animal product or by product, any source such as emulsifier, stabilizing agent, softening agent, function dressing etc.Be used for cereal of the present invention and comprise all plants that are considered to " cereal " crop, no matter it is used in the commercial agriculture at present still only is known as " cereal " in practice or on botany.For example, " cereal " comprises corn, wheat, rice, barley, Chinese sorghum, grain, oat, rye, triticale, buckwheat, Fu Niao (fonio) and quinoa (quinoa).Those of skill in the art will recognize that in given food compositions it is normal using one or more such bread baskets.Be used for meat of the present invention and comprise the product from any animal, preferred muscular tissue such as chicken and other poultry, lamb meat, sheep, veal, beef or pork.Be used for other animal product and by product of the present invention and comprise dairy products or by product from the milk of any species.Component or composition that other are important comprise fat, and those skilled in the art will appreciate that vegetables, animal or the microorganism fat in many sources can be used for the synthetic food composition.In one embodiment, the source of fat is plant fat such as corn, soybean or Tower rape oil, preferably obtains easily.In another embodiment, animal tallow such as butter are used to provide the calorie from fat, and are used for tarting up to carnivore.Certainly, being combined as of any aforementioned composition (as fat) is known in the art, and is used for the optimization food compositions based on functional character and price and availability.
Those skilled in the art also will appreciate that in preparation during composition of the present invention, but the composition varied slightly, make allow formulator consider the price of some composition in the composition and/or availability and in the analysis of some composition batch between variation.Thereby given food compositions or the described factor of compound basis can batch between, between plant or or even season between varied slightly is arranged.Although be selected for the special component of the food compositions of preparation particular batch this variation is arranged, but total composition (for example, the analysis of protein, carbohydrate, fat, fiber or other components) can keep constant or substantial constant at least, for example, described consistent with label, as the statement and the assurance of the minimum percent or the largest percentage of specific components.
In other embodiment, if composition of the present invention comprise with in animal to one or more effectively LCPUFA, NORC and the MCTs of amount and the vitamin B group and antioxidant when being included in the described composition in the following: reduce or decline, minimizing or the prevention behavior relevant with the age of prevention social interaction changes, increases trainability, keeps optimum cerebral function, promotes learning and memory, reduces the memory loss, delays aging of brain, prevention or treatment apoplexy and prevention or treatment dementia.
Those skilled in the art can understand the amount that is fit to of the LCPUFA, the NORC that how to determine to be added into given composition and MCTs, vitamin B group, antioxidant and any other composition.When how best skilled formulator contain the particular composition, food of LCPUFA, NORC and MCTs and other component or pharmaceutical composition in decision preparation, the species that managing to make do resits an exam considers animal, age, size, weight, health etc.Other factors that preparation can be considered comprise that types of compositions (for example, pet food composition is to diet supplement), the required dosage (LCPUFA, NORC and MCTs) of each component, different animals to the average consumption of particular type composition (for example, based on species, body weight, activity/energy requirement etc.) and preparation said composition preparation condition, preferably, to be added into LCPUFA, the NORC of composition and the concentration of MCTs based on animal to energy and nutritional need calculating.When preparation during the present composition, based on the characteristic of required dosage and animal, the technical staff can determine LCPUFA, NORC and the amount of MCTs and the amount of other compounds or component in the composition in the food compositions for example.
For pet food with for the people consumes the food product prepared, the scope that the amount of LCPUFA accounts for the percentage of composition be preferably composition about 0.1% to about 13%, although bigger percentage can be provided.In multiple embodiments, the amount of LCPUFA is about 0.1% of a composition, 0.2%, 0.3%, 04%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3.0%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, 4.0%, 4.1%, 4.2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8%, 4.9%, 5.0% or more, for example, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20% or more.Can use the LCPUFA of as many as 30,40 or 50% in certain embodiments.
For pet food with for the people consumes the food product prepared, the scope that the amount of MCTs accounts for the percentage of composition be preferably composition about 1% to about 30%, though littler, bigger percentage can be provided.In multiple embodiments, described amount is about 1.0% of a composition, 1.5%, 2.0%, 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, 10%, 10.5%, 11%, 11.5%, 12%, 12.5%, 13%, 13.5%, 14%, 14.5%, 15%, 15.5%, 16%, 16.5%, 17%, 17.5%, 18%, 18.5%, 19%, 19.5%, 20%, 20.5%, 21%, 21.5%, 22%, 22.5%, 23%, 23.5%, 24%, 24.5%, 25%, 25.5%, 26%, 26.5%, 27%, 27.5%, 28%, 28.5%, 29%, 29.5%, 30% or more.Can prepare the MCTs of diet supplement with the higher concentration that comprises several times, be used for animal being used with tablet, capsule, liquid concentrate or other similar formulations, or dilution before using, for example in water, dilute, spraying or spreading on pet food, and other similar methods of application.For diet supplement, independent MCTs can directly use or directly apply in the general food of animal to animal.The diet of multiple embodiments replenishes formulation and comprises about 30% to about 100% MCTs, though also can use amount still less.
For pet food with for the people consumes the food product prepared, the scope that the amount of NORC accounts for the percentage of composition be preferably composition about 0.1% to about 12%, though bigger percentage can be provided.In multiple embodiments, the amount of NORC is about 0.1% of a composition, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3.0%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, 4.0%, 4.1%, 4.2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8%, 4.9%, 5.0% or more, for example, 6%, 7%, 8%, 9%, 10%, 11%, 12% or more, as many as about 15% or even 20%.In specific embodiment, use the LCPUFA of 2-2.5% and the NORC of 2-2.5%.In described embodiment, pure product L-arginine is preferred NORC compound.Can prepare LCPUFA and the NORC of diet supplement with the higher concentration that comprises several times, be used for animal being used with tablet, capsule, liquid concentrate, emulsion, supensoid agent, gel or other similar formulations, or dilution before using, for example in water, dilute, or (for example add pet food, by spraying or spreading thereon), and other methods of application that are fit to use described diet supplement.
In as the embodiment of selecting, LCPUFA in the composition and the amount of NORC are the functions of the amount that realizes that in animal blood serum the specific concentrations of LCPUFA and/or NORC or its metabolite or the concentration range that needs are required.Skilled person in the art will appreciate that the specific concentrations of LCPUFA in the serum and/or NORC or need that range of concentrations can the LCPUFA of the recommended amounts that above describes in detail and the animal blood serum level of NORC be calculated by having measured feeding.
In preferred embodiments, food compositions comprises the macronutrient composition of the suitable food type of planning.In one embodiment, food compositions has about protein of 20 to 32%, about carbohydrate of 30 to 50%, about 5% to 20% fat and about moisture of 15% to 25%.In another embodiment, food compositions is pet food composition such as high-quality or extra best best pet food composition.In one embodiment, pet food is for dog class configuration and have about 20-30%, preferably about 24-28% and the protein content of 25-27% more preferably from about.In one embodiment, the protein content of dog food composition is about by weight 26%.Composition is the cat preparation in another embodiment, and has about 35-45%, preferably about 37-42% and the protein content of 39-41% more preferably from about.In one embodiment, the protein content of cat foods composition is about 40%.In preferred embodiments, composition be contain LCPUFA, NORC and MCTs and also comprise about 15% to about 50% protein, about 5% to about 40% fat, about 5% to about 10% content of ashes and food product with moisture of about 5% to about 20%.
In one embodiment, this food compositions is a wet provision, for example canned food, frozen food or fresh food.In one embodiment, this food compositions is an ambient stable.In another embodiment, it must refrigerate.In other embodiments, this food compositions is above-mentioned moderate amount of moisture product or dry food.
In preferred embodiments, LCPUFA is that fish oil and NORC are arginine or its nitric oxide release property derivative.In certain embodiments, composition comprise about 0.1% to about 50% fish oil and about 0.1% to about 20% arginine.In preferred embodiments, when composition was food product, LCPUFA and NORC were in the preferred range that this paper provided.Described scope provides the palatability and the functional character that can strengthen the Receptive improvement of food product.Preferably MCTs is also in preferred range.Excessive MCTs may have adsorbable oil packaging material is soaked into or painted trend, therefore, should make suitable selection for the packing of food compositions.
In multiple embodiments, composition is people's food compositions, pet food composition or diet supplement.Contain the concentration of LCPUFA, NORC and MCTs and amount and food product or pet food as the composition of diet supplement a great difference can be arranged.Usually, palatability and similar sensation factor are not had a meaning concerning certain diet supplement, for example, and the diet supplement that those are swallowed.
In one embodiment, LCPUFA comprises one or more natural fish oil, ALA, EPA, DPA, DHA or from the other n-3 fatty acid in any source.Certainly plan with the applied in any combination in LCPUFA source in this paper.N-3 or n-6LCPUFA also are intended for use in the multiple embodiments.
Preferably, be companion animals for example dog or cat compositions formulated.In other embodiment, animal is the people who has or the cognition relevant with the age to descend.
In one embodiment, compositions formulated to be providing every day about 0.5g to each LCPUFA and the NORC of about 10g, and it is divided into the recommendation doses of portion or many parts.For example, take for twice, can make every part of recommended amounts (for example, part of an amount of 2 spoons or a 20g, etc.) that each LCPUFA of 5g and the dosage that NORC provides 10g are provided by compositions formulated if composition is prepared every day.
In preferred embodiments, composition comprises about 0.1% medium chain triglyceride to about 30% formula 1, wherein with R ', the R " and R " of glycerol backbone esterification ' each independently has the fatty acid of 5-12 carbon naturally; About 0.1% to about 50% fish oil; With about 0.1% to about 20% arginine.Preferably, composition further comprises the vitamin B group of about 0.1 to 40 times recommendation daily requirement or about 0.1 to 25 times day recommends the antioxidant of requirement, or comprises the two.
In one embodiment, the composition that is used for method comprises about 10g to MCT, the about 0.5g of the about 30g LCPUFA of about 10g and the about 0.5g NORC of about 10g extremely extremely, and it comprises or do not comprise vitamin B group and the antioxidant of RDA.
In yet another aspect, described composition further comprises one or more cognitive medicines of the amount of effective enhancing cognitive function.Based on the given medicine recommended dose of drug manufacturer or based on the weight of animal, species, age, health status etc., those skilled in the art can determine to be added into the amount of the cognitive medicine in the described composition.
In yet another aspect, the invention provides the pharmaceutical composition that comprises the present composition and one or more pharmaceutically suitable carrier, dilution or excipient.Usually, pharmaceutical composition by with compound or composition and excipient, buffer, adhesive, plasticizer, colouring agent, thinner, compression agent, lubricant, flavouring, wetting agent etc., comprise that known can be used for of those of skill in the art produce other compositions of medicine and mix and prepare and be suitable for preparing for the composition of animal as medicament administration.Randomly, pharmaceutical composition further comprises one of vitamin B group and antioxidant or the two.
In yet another aspect, the invention provides the method that is used to strengthen the animal cognitive function.Described method generally includes one or more long-chain polyunsaturated fatty acids (LCPUFA) from the amount that comprises effective enhancing animal cognitive function to animal, one or more medium chain triglycerides (MCTs) and one or more nitric oxide release property compounds (NORC) of using.In certain embodiments, composition further comprises one or more vitamin B group, one or more antioxidants or its combination.
In some embodiments, LCPUFA, MCTs, NORCs, vitamin B group and antioxidant are administered to animal with amount given when this paper describes composition.In one embodiment, use composition with effective amount that increases one or more cognitions, motion or the behavioral function of animal, described animal comprises the healthy animal of institute's has age or easily suffers from or suffer from the animal of the cognitive function decline that is caused by ageing process or disease.In another embodiment, with effective prevention, reduce or delay animal, particularly easily suffer from or suffer from the amount that the animal cognitive function of the aging that the cognitive function that caused by ageing process or disease descends descends and use composition.In certain embodiments, the daily dose scope of composition for the about 5mg/ of each animal days to about 5,000mg/ days, 10,000mg/ days or 20,000mg/ days or more.Preferably, the daily dose scope for the about 30mg/ of each animal days to about 10,000mg/ days, and more preferably extremely about 7 for the about 750mg/ of each animal days, 500mg/ days.The daily dose of LCPUFA, NORC and MCTs can LCPUFA, NORC and the mode of gram number/kg the weight of animals (BW) of MCTs measure.The daily dose scope of LCPUFA, NORC and MCTs can be about 0.001g/kg to about 50g/kg animal BW, though higher or lower dosage can be provided.Preferably, the daily dose of LCPUFA, NORC and MCTs is that about 0.001g/kg is to about 25g/kg animal BW.More preferably, the daily dose of LCPUFA, NORC and MCTs is that about 0.001g/kg is to about 10g/kg animal BW.More preferably, the daily dose of LCPUFA, NORC and MCTs is that about 0.001g/kg is to about 5g/kg animal BW.More preferably, the daily dose of LCPUFA, NORC and MCTs is that about 0.001g/kg is to about 1g/kg animal BW.More preferably, the daily dose of LCPUFA, NORC and MCTs is that about 0 001g/kg is to about 0.5g/kg animal BW.
According to using of described method can be on needed or desirable basis, adopts frequency that change or rule.Clocklike She Qu purpose is to provide the direct and indirect metabolite that is produced with maybe this picked-up of composition of consistent dosage rule for animal.Described rule will be tending towards obtaining the component of constant composition or the blood level of their direct or indirect metabolite with consistent dosage.Thereby using of rule can be that 1 time every month, 1 time weekly, every day 1 time or every day are more than 1 time.Similarly, using can be every other day, week or month, per three days, week or month, per four days, week or month etc. carry out.Use can be every day repeatedly.When being used as the fill-in of full diet needs, composition can directly be applied to animal, for example by oral or other modes.Alternatively, can or mix composition and daily feed or food (comprising liquid) contact, or the animal of accepting described disposal is carried out intravenous injection as drinking water.When as daily feed or food, using can be known for those of ordinary skill.
Using can also be as the part of animal diet followed scheme and carry out.For example, diet program can comprise the composition as herein described of amount of the reduction of one or more cognitions, motion or the behavioral function that make animal absorb effective prevention regularly, reduce or delay animal.
According to method of the present invention, the using of composition (comprising using as the part of diet program) can be crossed over childbirth by animal to running through the adult time period.In multiple embodiments, animal is people or companion animals such as dog or cat.In certain embodiments, animal is an animal young or that growing.In a more preferred embodiment, animal is old and feeble animal.Usually preferably reach about 35% animal of its planned life.In present embodiment preferred, when animal has reached about 30%, 40% or 50% when above of its plan or life expectancy, for example use based on clocklike or long-term application program clocklike begin.In some embodiments, animal has reached 40,45 or 50% of its life expectancy.In other embodiment, animal is older, and it has reached 60,66,70,75 or 80% of its possible life-span.The mensuration in life-span can be based on insurance actuarial table, calculating or estimation etc., and can consider known the life-span to be played the past of front or negative effect, current and following influence or the factor.When measuring the life-span, species, sex, size, inherent cause, environmental factor and stressor, health condition, the consideration with current nutrition condition, stressor etc. the past current and the past also can exert an influence or be considered.
In the multiple embodiments of method, composition is human food's composition, pet food composition or diet supplement.In other embodiment, composition is a food compositions, and it also comprises about 15% to about 50% protein, about 5% to about 40% fat, about 5% to about 10% content of ashes and has about 5% to about 20% moisture.
Preferably, the composition that is applied comprises about 1% to about 30% MCTs.In addition, preferred MCTs structural group becomes that to surpass R ', R " and R " ' length of about 95% be 8 carbon.In certain embodiments, remaining R ', R " and R " ' be the fatty acid of 6-carbon or 10-carbon.
In certain embodiments, LCPUFA is that fish oil and NORC are arginine or its nitric oxide-release property derivative.MCTs preferably derives from cocoa butter, but can use other sources.
In certain embodiments, the composition that is applied comprises about 0.1% to about 50% fish oil and about 0.1% to about 20% arginine.For the embodiment of method, as above-mentioned composition, LCPUFA comprises one or more natural fish oil, ALA, EPA, DPA, DHA, n-3 fatty acid or its combination in other any source.
In one embodiment, the composition that uses in the method is prepared to provide about 0.5g each LCPUFA and NORC every day to about 10g via recommendation doses a or many parts.Described composition can further comprise one or more vitamin B group and one or more antioxidants.Vitamin B group preferably comprises about 0.1 to about 40 times RDA, and antioxidant accounts for about 0.1% to about 25% of composition.Preferably, composition comprises the mixture of vitamin B group.
In one embodiment, described composition is applied to animal together with effective one or more cognitive medicines that strengthen the amount of cognitive and relevant function mentioned above.In a specific embodiment, the composition of using is the pharmaceutical composition that comprises cognitive medicine and LCPUFA, NORC and MCTs.In preferred embodiments, composition by every day application program be applied to animal, preferably using with single dose.
In certain embodiments, animal is healthy aged animal.In other embodiment, animal has the phenotype of the Cognitive function damage relevant with the age.For example, when with the control-animal that does not have described phenotype relatively the time, the phenotype that described animal may have comprises: the reduction of memory ability, short term memory loss, pace of learning descend, learning ability descends, resolution ability technical ability descends, the attention span descends, locomitivity descends, confusion of consciousness increases or dull-witted (Alzheimer disease of philtrum or its in other animal be equal to illness) in one or more.
In yet another aspect, composition comprises effective LCPUFA, NORC and MCTs that improves the amount of one or more social actions.In preferred embodiments, animal is a companion animals.
Believe and after described composition is applied to animal, increase LCPUFA, NORC and the circulation composition of MCTs in animal blood or blood plasma.In certain embodiments, increased by the blood concentration of the resulting direct or indirect metabolite of the consumption of LCPUFA, NORC and/or MCTs, and can be used as the indication of dosage.In normal processes, also can appear at the decline of one or more compound concentrations in the blood flow of the animal of accepting described composition.Described decline also can be the useful tool that is used to detect or determine dosage.The variation of the amount of the blood flow component that preferably, measure is a dose dependent.In some embodiments, described method causes the increase of one or more ketoboidies in animal blood.Comprising additional compounds at described composition (for example, vitamin B group or antioxidant in) the embodiment, uses the increase of the circulation composition that causes these compounds and can be used as the indication of dosage.
The present invention also provides and has been used to influence various cognitions, motion or behavior function associated and is used to influence the various methods that relate to the physiologic function of cognition, motion or behavioral function, for example social interaction and aging of brain.Usually, described method comprises composition of the present invention is applied to animal with this paper to composition and the defined amount of method.
On the one hand, the invention provides the method that is used to reduce or prevent the decline of animal society's contacts, it comprises that the composition that will comprise LCPUFA, NORC and MCTs is applied to animal with the amount that effective minimizing or prevention social interaction descend.In preferred embodiments, composition further comprises one or more vitamin B group, one or more antioxidants of amount of decline of effective minimizing or prevention animal society contacts or the two.
In yet another aspect, the invention provides the method that is used to reduce or prevents the behavior relevant with the age of animal to change, it comprises LCPUFA, NORC and MCTs is applied to animal with the amount of effective minimizing or the prevention animal behavior variation relevant with the age.Preferably, the behavior relevant with the age to change be forgetful, disorientation, social interaction custom variation, " family training (housetraining) " forfeiture, confusion of consciousness of descending, sleeping and wake up, defeat or the disposition variation in one or more.Write down described variation in response to the cognition decline of people and other animals.In preferred embodiments, composition further comprises one or more vitamin B group, one or more antioxidants of the amount of effective minimizing or the prevention animal behavior relevant with age variation or the two.
In yet another aspect, the invention provides the method that is used to increase the animal trainability, it comprises that the composition that will comprise LCPUFA, NORC and MCTs is applied to animal with the amount of effective increase trainability.For example, when baby, doggie and kitten are carried out toilet training,, use composition and make that the animal learning task is rapider if train and compare with not using composition.Similarly, when training dog or cat obey oral, signal or other order,, use composition and make that the animal learning task is rapider if train and compare with not using composition.Similarly, composition can be used to train feral or the pet of wildlife as being used for circus wagon animal or catching in the open air.In preferred embodiments, composition further comprises one or more vitamin B group, one or more antioxidants of the amount of effective increase animal trainability or the two.
In yet another aspect, the invention provides the method that is used to keep the optimum cerebral function of animal.Described method comprises that the composition that will comprise LCPUFA, NORC and MCTs is with effective prevention or delay the amount that cerebral function descends, particularly descends in time and be applied to animal.In preferred embodiments, composition further comprises one or more vitamin B group, one or more antioxidants of the amount of the optimum cerebral function of effective maintenance animal or the two.
In yet another aspect, the invention provides the method that is used to promote animal learning and memory.Described method comprises that the composition that will comprise LCPUFA, NORC and MCTs is applied to animal with the amount of effective promotion animal learning and memory.In one embodiment, described animal reached its life expectancy at least about 50%.In preferred embodiments, composition further comprises one or more vitamin B group, one or more antioxidants of the amount of effective promotion animal learning and memory or the two.
In yet another aspect, the invention provides the method that is used to reduce animal memory loss.Described method comprise will comprise the composition of LCPUFA, NORC and MCTs be applied to animal with the amount of effective minimizing memory loss in time.In preferred embodiments, composition further comprises one or more vitamin B group, one or more antioxidants of the amount of effective minimizing animal memory loss or the two.
In yet another aspect, the invention provides and be used to delay the aging method of animal brain.Described method comprises that the composition that will comprise LCPUFA, NORC and MCTs is applied to animal effectively to delay the aging amount of animal brain.In preferred embodiments, composition further comprises one or more vitamin B group of effectively delaying the aging amount of animal brain, one or more antioxidants or the two.
In yet another aspect, the invention provides the method that is used to prevent or treat the animal apoplexy.Described method comprises that the composition that will comprise LCPUFA, NORC and MCTs is applied to animal with the amount of effective prevention or treatment apoplexy.In preferred embodiments, composition further comprises one or more vitamin B group, one or more antioxidants of the amount of effective prevention or treatment animal apoplexy or the two.Described method is based on following discovery: reduce the apoplexy infringement that causes and some aspect that strengthens cognitive function and for example reduce memory and lose relevant.
In yet another aspect, the invention provides the method that is used to prevent or treat the animal dementia, described method comprises that the composition that will comprise LCPUFA, NORC and MCTs is applied to animal with effective prevention or the dull-witted amount of treatment.In preferred embodiments, composition further comprises one or more vitamin B group of amount, one or more antioxidants of effective prevention or treatment animal dementia or the two.Dementia can be people's Alzheimer disease (AD), the dog cognition dysfunction syndrome (CCDS) of dog class or the similar disease of other animal.Described method is based on following discovery: the compositions and methods of the invention prevent by the influence that reduces the infringement that is caused by dull-witted reason or reduce dementia, for example, and the deterioration of amyloid beta deposition or arterial function.
The behavior relevant with the age in the decline that is used for reducing or preventing social interaction, minimizing or prevention changes, increases trainability, keeps optimum cerebral function, promotes learning and memory, reduces to remember and lose, delay aging of brain, prevention or treatment apoplexy and prevention or the dull-witted method of treatment, animal is people or companion animals preferably, most preferably dog or cat.The amount of employed LCPUFAs, NORCs, MCTs, vitamin B group, antioxidant and other compositions is with identical or in its scope for strengthening the given amount of cognitive function in these methods.
In yet another aspect, the invention provides the cover box that the composition that is suitable for comprising one or more LCPUFAs, NORCs and MCTs is applied to animal.(be determined by circumstances) in the container that separates of described cover box in individual packaging or in the container that separates in virtual package and comprise (a) one or more LCPUFAs according to cover box component, (b) one or more NORCs, (c) one or more MCTs, and one or more (1) one or more be suitable for other compositions of animals consuming, (2) one or more vitamin B group, (3) one or more antioxidants, (4) one or more cognitive medicines, (5) one or more prebioticses, (6) one or more probios, (7) one or more are suitable for judging whether animal can be from being used for strengthening the composition of cognitive function and function associated and the diagnostic device that method benefits, (8) illustrate how to make up or the LCPUFA that provides at the cover box that is used for being applied to animal is provided, the specification of NORC and MCTs and other compositions, (9) illustrate the cover box component of how animal advantageously being used combination, the specification of the cover box component of preparation or other cover box components and (10) are used for cover box component applied combination or preparation in the device of animal.Provide in the container that separates in each comfortable individual packaging of described component or provide with the mixture of the various components in Different Package.In preferred embodiments, the cover box comprises LCPUFAs, NORCs, MCTs, vitamin B group and antioxidant.Described cover box can comprise the composition with various combining forms.For example, described cover box can be included in mixture of one or more vitamin B group and one or more antioxidants in the container and one or more other composition in one or more other containers.Similarly, described cover box can be included in LCPUFA and the mixture of MCTs and one or more other composition in one or more other containers in the container.Other such combinations can prepare based on the characteristic of composition and their physics and chemical property and compatibility by those skilled in the art.
In yet another aspect, the invention provides be used for passing on about the following one or more information or to its means of explanation: (1) is used to strengthen the composition of the present invention of cognitive function, (2) LCPUFAs of the present invention, NORCs, MCTs, vitamin B group, antioxidant or other components are mixed with preparation be applicable to the composition that strengthens cognitive function, the cover box of the present invention that (3) are used to strengthen cognitive function is applied to animal with (4) with described composition.Described means comprise one or more the physics that comprises information and explanation or electronic document, digital storage medium, optical storage medium, audio presentation, audiovisual display or visual display.Preferably, described means be selected from displaying website, visual display booth, publicity materials, Product labelling, package insert, advertisement, distribute material, bulletin, audio tape, record-reproduce head, DVD, CD-ROM, computer-readable chip, computer-readable card, computer-readable disk, USB device, FireWire device, computer storage and any combination thereof.
In yet another aspect, the invention provides to be used to prepare and comprise the method for food compositions that LCPUFA, NORC, MCTs and one or more are suitable for other compositions of animals consuming, described other compositions for example are protein, fat, carbohydrate, fiber, vitamin B group and antioxidant.Described method comprises mixes one or more compositions that is suitable for animals consuming and LCPUFA, NORC and MCTs and possible other compositions such as vitamin B group and/or antioxidant.Perhaps, described method comprises LCPUFA, NORC and MCTs and other compositions if desired the time put on the food compositions individually or with any in combination, for example, and as dressing or batching (topping).LCPUFA, NORC and MCTs can add in the preparation and/or any time in the process of food compositions.It for example comprises, LCPUFA, NORC and MCTs is mixed as the part of the nucleus of food compositions " main body " or they are applied as dressing, promptly mainly is coated to the surface of food compositions after its preparation.Described composition can be according to any suitable method preparation in this area.
In yet another aspect, the invention provides the packing that comprises composition of the present invention and invest the label on the packing, described label comprises word or phrase, picture, design, initialism, poster, phrase or other devices or their combination, it has indicated to comprise in the described packing and has been applicable to animal, particularly strengthen cognitive function in the Shuai Lao animal, reduce or prevent the decline of social interaction, minimizing or prevention age, relevant behavior changed, increase trainability, keep optimum cerebral function, promote learning and memory, reduce the memory loss, delay aging of brain, prevention or treatment apoplexy or prevention or the dull-witted composition of treatment.Usually, the described device statement that is equal to that comprises that phrase " improves cognitive function ", printed on " improve memory ", " reducing the memory loss of old and feeble animal " or the packing.Any packing or packaging material that are fit to comprise described composition can be used for the present invention, for example, and the bag of making by paper, plastics, paper tinsel, metal etc., box, bottle, jar, deck etc.In preferred embodiments, comprise the food compositions that is applicable to particular animals such as people, dog class animal or cats (sighting target sign and decide), preferably the companion animals food compositions.
The purposes of the medicine of in yet another aspect, the invention provides that LCPUFA, NORC and MCTs change in the relevant behavior of decline, minimizing or prevention age that preparation is used for strengthening animal cognitive function, minimizing or prevention social interaction, increase trainability, keep optimum cerebral function, promote learning and memory, reduce the memory loss, delay aging of brain, prevention or treatment apoplexy and prevention or treatment are dull-witted.Described medicine further comprises one or more vitamin B group, antioxidant or its combination.Usually, mix by other compositions of compound or composition and excipient, buffer, adhesive, plasticizer, colouring agent, thinner, compression agent, lubricant, flavouring, wetting agent and known can be used for of those of skill in the art being produced or prepared the medicine that is suitable for being administered to animal and prepare medicine.
In the present invention, described animal can be childhood, adult, older or old and feeble animal.Usually for most of embodiments, described animal is old and feeble animal.Usually, animal is a senior animal in the second half of its life expectancy, last 1st/4th, the old and feeble animal of its life expectancy.The life-span definition changes according to various animals, and is known to the those skilled in the art.For example, before 16 years old age, be considered to be in the animal of childhood.For dog or cat, it is in childhood before thinking 1 years old.
Use multiple use approach that composition of the present invention is applied to animal, described composition comprises pharmaceutical composition and medicine.That described approach comprises is oral, in the nose, in the intravenous, intramuscular, stomach, pylorus, subcutaneous, rectum etc.Preferably composition oral is used.
Composition of the present invention is applied to animal, it continues to finish the needed time of one or more target of the present invention, described composition comprises pharmaceutical composition and medicine, and described target of the present invention for example strengthens cognitive function, minimizing or prevention social interaction in animal decline, minimizing or the prevention behavior relevant with the age changes, increases trainability, keeps optimum cerebral function, promotes learning and memory, reduces the memory loss, delays aging of brain, prevention or treatment apoplexy and prevention or treatment dementia.Described composition is suitable for chronic administration or according to using with any scheme of composition and goal congruence.
Embodiment
The present invention can further set forth by following examples, though be understood that: except as otherwise noted, otherwise in described embodiment only was included in for the purpose of illustration, it was not in order to limit the scope of the invention.
Embodiment 1
Animal and test group
The beagle that test 48 has only cognitive experience (23 male and 25 female, the age is 7.5 to 11.6 years old).Its mean age is 9.38.For qualified, described dog must have at least 6 months recognition tests experience in the past, comprises postponing non-matched position task (delayednon-matching-to position task) (DNMP) and distinguish different task (oddity task) training.
In initial baseline period, all dogs are provided estimate the DNMP task (if or when failing before to learn this task then at 5s) of variable delay version of the means of visual space working memory, and size discrimination and inverse task.Utilization is divided into dog disposal group suitable in four cognitions in the performance on these tasks: (1) 5.5%MCT group, (2) 12.5%MCT group, the selenium (" uniting the disposal group ") of the vitamin E of the vitamin B group of (3) 12.5%MCT and 2% fish oil, 2.5% arginine, 1 to 40 times of RDA, the vitamin C of 150mg/kg, 900mg/kg and 05mg/kg and (4) control group.
Feed and water
Dog can drink water at any time via automatic water supply system of installing on the wall and/or bucket.Provide a kind of in five kinds of adults maintenance foods to animal once a day, it has about 32% protein, 20% fat and 3% fiber.Initial individual quantity of food is used formula " kilocalorie=110 kilocalorie/day x (BW x 075) that needs ", and wherein BW is a body weight.Keep constant body weight under the health that described formula is intended to be fit to.
Beginning in treatment is weighed to dog weekly, and weighs twice in the stable back of food intake and health to its every month, and constant relatively body weight is required adjusts food intake according to keeping.Give the animal food that feed in about 30 minutes is given.The general amount of record leftover in the food intake record sheet of each animal.
Living conditions
Cognitive series of tests
Sign is distinguished study (7-99 day).Self-centeredness study and reverse (Egocentrie learningand reversal) (100-163 day)
Sign differentiation task
In this task, dog goes near one in two targets based on the degree of closeness of itself and trappings in training.This task is intended to estimate allocentric spacial ability, and the outside sign of its requirement utilization is located the target in the space.Test each dog with the version that the difficulty of same common question increases successively.
The universal test flow process: every day to each dog carry out 10 times the test, test bay be 30 seconds at interval.Carry out 1 test every day, about weekly 6 times, so carry out 80 phases altogether.Use the part correction method.In the method, allow dog making mistakes back their reaction of correction once at each issue.According to the success that dog is obtained, every dog is carried out the test of four problems at most when dealing with problems.For carrying out forward from first and second problems, dog must be finished a two stage standard.For by first stage, dog must have at least 9 secondary responses correct in 10 tests, or must have 8 secondary responses correct in going through 10 times continuous two days tests.Dog must be made a response to pass through the phase I in all tests.When dog has at least 70% reaction correct, finish second standard stage in ensuing 30 tests going through continuous three phases.Give 0.5 mark to the dog that in any one test, does not do reaction, think that it is based on the reaction of selecting at random, and one day test is to finish described 30 tests.Requiring average score value by second stage is 70% of all test day.
The sign of distinguishing is the same white pulvinulus and the timber (2cmx2cmx9cm) of yellow as a token of.The little planchet of each white is placed the top, food hole of the both sides of presenting on the pallet.Being fixed signal in place, is that the little band of each Velcro (velcro) of 2cm is adhered to the position that is fit on the top center of pulvinulus and the meal tray with diameter.
Initial mark test (sign-0): in initial testing (L0), sign is tied up to one center in two white pulvinuluses.In each test, put award food in the food hole on experimenter's on the left side or the right, and correspondingly place described sign.Door is risen and pallet is moved to from the about 25cm of dog place, have the time interval of of short duration close examination to make dog can see the spatial arrangement on the pallet.Give dog with pallet then, and allow dog to make a response.On this level and all levels subsequently, require dog that the pulvinulus that approaches to indicate is made a response and obtain the food award.Determine that by computer random ground a correct side, condition are is correct in half test in each test of each testing period of each side.During L0, allow every dog to carry out 30 maximum testing periods (300 tests) and learn the stimulation relevant with sign made a response.
Remedy training: the dog to failure in initial L0 test is remedied training program to help to instruct their described tasks.Remedy training and form 25 tests every day by the training in 5 days that add.Remedying the beginning of training, stimulating in the great majority test, for the single award of animal.In the test that continues, give other couple stimulation.Finish remedy the learning period after, animals received other training, carried out for 10 phases at most, it uses initial scheme.This scheme also is used for the dog of failing at L1.The dog of failing in L0 proceeds to L1 forward.If 80 testing periods do not finish as yet, then the dog of remedying failure to train behind L1 proceeds to next task.If residue 10 testing periods of less than, then the animal of L1 obtains the extra training period of remedying.
Sign-1 (L1): in case dog has been learned L0 task (during initial training or remedying training back), inwardly just will indicate and move 1cm and away from the pulvinulus edge that it has constituted and indicates 1 (L1) to the diagonal angle.The Velcro band wide with the 2cm of black is tied to sign on the meal tray.To remedying training the 30 interim not dogs of association, as above to as described in the L0.
Self-centeredness testing scheme (Egocentric Test Protocol)
Universal testing method: when on-test, open the door that hinge is housed and come, and allow dog to make a response by one in mobile two identical stimulations at most at 30 seconds to dog stimulus pallet.When dog has been moved the The food stimulation thing of covering award, calculate a correct response.When moving the stimulation that does not have award, dog calculates a mistake.The period of 63 phases of animals received, each issue 12 tests.
The preferred stage: the preferred test of dog being carried out being made of the discrete test of using the target that covers food hole, both sides in first day in test determines whether to exist any preferential side.With the positive side of preferential side as the initial acquisition phase of test.Therefore, if animal is selected the target on its left side the most continually, the left side with animal is decided to be its preferential side so.For the animal that does not show preferential side (and all react 5 time both sides), with inserting coins to determine to reward side.
Obtain the stage: each test is presented by the single of the stimulation dish of the stimulus with the side opening that covers preferential side or centre bore and constitutes.Second non-award stimulation target covers the hole of the not preferred side of dog.Therefore from animal preferential side target farthest award is always arranged.In any given test, three kinds of possible spatial configuration (left side-center, left and right or right-center) are arranged.Each configuration occurs 4 times in each testing period.
Standard: in case dog when three continuous testing periods obtain minimum 90% accuracy (36 tests 33 times correct), the stage of obtaining completes successfully.Give maximum 12 phases or 144 tests to satisfy this standard.If animal then gives the training of remedying of 5 phases in 12 interim not association, carry out extra maximum 10 phases then.
Reversal phase:, just will reward the position and be changed to opposition side in case animal has passed through the stage of obtaining.Thereby, in obtaining test,, then in opposite test, will be made as award near the target in its left side if will be made as award near the target on dog right side.For the negative testing first time, the study standard is identical when obtaining at first.Give maximum 15 phases or 180 tests to satisfy this standard.If animal is not interimly satisfied standard 15, then give the training of remedying of 5 phases.Extra 10 phases of animals received are to reach the study standard then.
(repeatedly) reversal phase that repeats: in case Zoological Society initial oppositely, just a correct side is changed, and animal is tested until it again learn this task again.Repeat this process and in the self-centeredness scheme, finish 52 phases altogether until animal.The result is shown in following each table.
Sign mapping test result
Table 1 sign-0 test result
According to data show, the performance of control group is poorer than other each groups.
Table 2 sign-1 test result
Figure GPA00001087146900372
Control group and 5.5%MCT group, 12.5%MCT group and to unite the disposal group significantly different.Compare with any other group, all performance is better on two tasks to unite the disposal group, has shown synergistic effect.
The self-centeredness test result
Table 3 obtains test result
Figure GPA00001087146900373
??12.5%MCT ??15.92 ??2.61
The associating disposal ??12.82 ??2.23
According to data show, control group and 5.5%MCT group and to unite the disposal group significantly different.
The anti-phase test result of table 4
Figure GPA00001087146900381
According to data show, control group and 12.5%MCT group and to unite the disposal group significantly different.Associating disposal group is also significantly different with the 5.5%MCT group.The performance numerically of associating disposal group is all better than any other group, demonstrates unforeseeable and collaborative effect.
The anti-phase test result that table 5 repeats
Figure GPA00001087146900382
According to data show, control group is significantly different with every other disposal group.The effect that all treatments are all useful.In general, the compound (it comprises LCPUFA, NORC and MCTs) that above data show is applied to associating disposal group has influenced cognitive function, and has shown owing to using this combination and obtained unforeseeable effect, comprises some synergistic effects.
In specification, common embodiment preferred of the present invention is disclosed.Although the use particular term, they only use with general and descriptive sense rather than are restrictive.In following claim, set forth protection scope of the present invention.Significantly, according to above-mentioned instruction, can make many improvement and variation to the present invention.Therefore it being understood that within the scope of the appended claims, can be different from concrete described enforcement the present invention.

Claims (115)

1. be applicable to the composition that strengthens the animal cognitive function, it comprises one or more long-chain polyunsaturated fatty acids (LCPUFA), one or more medium chain triglycerides (MCTs) and one or more nitric oxide release property compounds (NORC) of the amount of effective enhancing animal cognitive function.
2. the composition of claim 1, wherein animal is people or companion animals.
3. the composition of claim 2, wherein companion animals is canid or cats.
4. the composition of claim 1, wherein animal is old and feeble animal.
5. the composition of claim 1, wherein LCPUFA comprises one or more natural fish oil, ALA, EPA, DPA, DHA or from the other n-3 fatty acid in any source.
6. the composition of claim 1, wherein LCPUFA is a fish oil.
7. the composition of claim 1, it comprises about 0.1% to about 50%LCPUFA.
The composition of 8 claims 1, wherein MCTs can be represented by following general formula (formula 1):
Wherein with R ', the R " and R " of glycerol backbone esterification ' each independently has the fatty acid of 5-12 carbon atom naturally.
9. the composition of claim 8, wherein surpass about 95% R ', R " and R " ' length be 8 carbon.
10. the composition of claim 9, wherein remaining R ', R " and R " ' are the fatty acid of 6-carbon or 10-carbon.
11. the composition of claim 1, it comprises about 1% to about 30%MCTs.
12. the composition of claim 1, wherein NORC is arginine or its nitric oxide-release property derivative.
13. the composition of claim 1, it comprises about 0.1% to about 20%NORC.
14. the composition of claim 1, it further comprises one or more vitamin B group of the amount of effective enhancing cognitive function.
15. the composition of claim 14, it comprises the vitamin B group of about 0.1 to 40 times recommendation daily requirement.
16. the composition of claim 1, it further comprises one or more antioxidants of the amount of effective enhancing cognitive function.
17. the composition of claim 16, it comprises the antioxidant of about 0.1 to 25 times recommendation daily requirement.
18. the composition of claim 1, it further comprises one or more vitamin B group and one or more antioxidants of the amount of effective enhancing cognitive function.
19. the composition of claim 18, it comprises the vitamin B group of about 0.1 to 40 times recommendation daily requirement and the antioxidant of about 0.1 to 25 times recommendation daily requirement.
20. the composition of claim 1, it is configured to human food's composition, pet food composition and diet supplement.
21. the composition of claim 20, wherein composition be further comprise about 15% to about 50% protein, about 5% to about 40% fat, about 5% to about 10% content of ashes and food compositions with moisture of about 5% to about 20%.
22. the composition of claim 1, it further comprises one or more cognitive medicines of the amount of effective enhancing cognitive function.
23. the composition of claim 22, wherein cognitive medicine are one or more selegilines, Nicergoline, phosphatidylserine, Propentofylline, galanthamine, vinpocetine, donepezil, biloba extract thing, bisphosphonates, Raloxifene, oestrogenic hormone, calcitonin, Risedronate or the Alendronate of the cognitive amount of effectively influence.
24. the composition of claim 1, it further comprises one or more prebioticses or probio.
25. composition, it comprises the medium chain triglyceride of about 0.1% to about 30% formula 1, wherein with the glycerol backbone esterification R ', R " and R " ' each independently has the fatty acid of 5-12 carbon naturally; About 0.1% to about 50% fish oil; With about 0.1% to about 20% arginine.
26. the composition of claim 25, it further comprises the vitamin B group of about 0.1 to 40 times recommendation daily requirement and the antioxidant of about 0.1 to 25 times recommendation daily requirement.
27. pharmaceutical composition or alimentation composition, but it comprises the composition of claim 1 and carrier, thinner or the excipient that one or more are pharmaceutically acceptable or nutrition is used.
28. be used for the method that animal strengthens cognitive function, it comprises that the composition that will comprise one or more long-chain polyunsaturated fatty acids (LCPUFA), one or more medium chain triglycerides (MCTs) and one or more nitric oxide release property compounds (NORC) is applied to animal with effective amount that strengthens the animal cognitive function.
29. the method for claim 28, wherein animal is people or companion animals.
30. the method for claim 28, wherein companion animals is canid or cats.
31. the method for claim 28, wherein animal is old and feeble animal.
32. the method for claim 28, wherein LCPUFA comprises one or more natural fish oil, ALA, EPA, DPA, DHA or from the other n-3 fatty acid in any source.
The method of 33 claims 28, wherein LCPUFA is a fish oil.
34. the method for claim 28, wherein composition comprises about 0.1% to about 50%LCPUFA.
35. the method for claim 28, wherein the MCTs structure is a formula 1, wherein with R ', the R " and R " of glycerol backbone esterification ' each independently has the fatty acid of 5-12 carbon atom naturally.
36. the method for claim 35, wherein surpass about 95% R ', R " and R " ' length be 8 carbon.
37. the method for claim 36, wherein remaining R ', R " and R " ' are the fatty acid of 6-carbon or 10-carbon.
38. the method for claim 28, wherein composition comprises about 1% to about 30%MCTs.
39. the method for claim 28, wherein NORC is arginine or its nitric oxide-release property derivative.
40. the method for claim 28, wherein composition comprises about 0.1% to about 20%NORC.
41. the method for claim 28, wherein composition further comprises one or more vitamin B group of the amount of effective enhancing cognitive function.
42. the method for claim 41, wherein composition comprises the vitamin B group of about 0.1 to 40 times recommendation daily requirement.
43. the method for claim 28, wherein composition further comprises one or more antioxidants of the amount of effective enhancing cognitive function.
44. the method for claim 43, wherein composition comprises the antioxidant of about 0.1 to 25 times recommendation daily requirement.
45. the method for claim 28, wherein composition comprises one or more vitamin B group and one or more antioxidants of the amount of effective enhancing cognitive function.
46. the method for claim 45, wherein composition comprises the vitamin B group of about 0.1 to 40 times recommendation daily requirement and the antioxidant of about 0.1 to 25 times recommendation daily requirement.
47. the method for claim 28, wherein composition is configured to human food's composition, pet food composition and diet supplement.
48. the method for claim 47, wherein composition be further comprise about 15% to about 50% protein, about 5% to about 40% fat, about 5% to about 10% content of ashes and food compositions with moisture of about 5% to about 20%.
49. the method for claim 28 is wherein with composition one or more cognitive medication combined animals that are applied to the amount that effectively strengthens cognitive function.
50. the method for claim 49, wherein cognitive medicine are one or more selegilines, Nicergoline, phosphatidylserine, Propentofylline, galanthamine, vinpocetine, donepezil, biloba extract thing, bisphosphonates, Raloxifene, oestrogenic hormone, calcitonin, Risedronate or Alendronate.
51. the method for claim 28, the composition of wherein using are pharmaceutical composition or the alimentation compositions that randomly comprises one or more cognitive medicines.
52. the method for claim 28, wherein composition is used by long-term application program clocklike.
53. the method for claim 52, wherein composition by every day application program use.
54. the method for claim 28, wherein animal is old and feeble animal.
55. the method for claim 54, wherein animal has the relevant phenotype of the Cognitive function damage relevant with the age.
56. the method for claim 55, wherein compare with the control-animal that does not have described phenotype, phenotype comprises: one or more in the reduction of memory ability, short term memory loss, pace of learning decline, learning ability decline, the decline of resolution ability technical ability, attention span decline, locomitivity decline, confusion of consciousness increase or the dementia.
57. the method for claim 28 is wherein used the increase that causes one or more ketoboidies in animal blood.
58. the method for claim 28, wherein animal is the animal of the aging of health.
59. be suitable for and comprise one or more LCPUFAs, the composition of NORCs and MCTs is applied to the cover box of animal, described cover box comprises (a) one or more LCPUFAs in the container that separates in individual packaging or in the container that separates in virtual package according to cover box component with being determined by circumstances, (b) one or more NORCs, (c) one or more MCTs, and one or more (1) one or more be suitable for other compositions of animals consuming, (2) one or more vitamin B group, (3) one or more antioxidants, (4) one or more cognitive medicines, (5) one or more prebioticses, (6) one or more probios, (7) one or more are suitable for judging whether animal can be from being used for strengthening the composition of cognitive function and function associated and the diagnostic device that method benefits, (8) illustrate how to make up or the LCPUFA that provides at the cover box that is used for being applied to animal is provided, the specification of NORC and MCTs and other compositions, (9) illustrate the cover box component of how animal advantageously being used combination, the specification of the cover box component of preparation or other cover box components and (10) are used for cover box component applied combination or preparation in the device of animal.
60. be used for passing on about the following one or more information or to its means of explanation: (1) is used to strengthen the composition of the present invention of cognitive function, (2) with LCPUFAs of the present invention, NORCs, MCTs, vitamin B group, antioxidant or other components are mixed the composition that is applicable to the enhancing cognitive function with preparation, (3) cover box of the present invention and (4) that are used to strengthen cognitive function are applied to animal with described composition, and described means comprise one or more physics that comprises information and explanation or electronic document, the digital storage medium, optical storage medium, audio presentation, audiovisual display or visual display.
61. the means of claim 60 be selected from displaying website, visual display booth, publicity materials, Product labelling, package insert, advertisement, distribute material, bulletin, audio tape, record-reproduce head, DVD, CD-ROM, computer-readable chip, computer-readable card, computer-readable disk, USB device, FireWire device, computer storage and any combination thereof.
Comprise the method for food compositions that LCPUFA, NORC, MCTs and one or more are suitable for other compositions of animals consuming 62. be used to prepare, described method comprises one or more compositions that is suitable for animals consuming and LCPUFA, NORC and MCTs mixes or LCPUFA, NORC and MCTs are put on the food compositions individually or with any in combination.
63. the method for claim 62, the composition that wherein is suitable for animals consuming are one or more vitamin B group, one or more antioxidants or the two.
64. be used to reduce or prevent the method for animal society's contacts decline, it comprises that the composition that will comprise LCPUFA, NORC and MCTs is applied to animal with the amount that effective minimizing or prevention social interaction descend.
65. the method for claim 64, wherein animal is people or companion animals.
66. the method for claim 64, wherein animal is old and feeble animal.
67. the method for claim 64, wherein composition further comprises one or more vitamin B group, one or more antioxidants or the two.
68. the method that is used to reduce or prevents the behavior relevant with the age of animal to change, it comprises LCPUFA, NORC and MCTs is applied to animal with the amount of effective minimizing or the prevention animal behavior variation relevant with the age.
It is forgetful, disorientation, social interaction custom variation, " family training " forfeiture, confusion of consciousness of descending, sleeping and wake up that 69. the method for claim 68, wherein relevant with age behavior change, defeat or the disposition variation in one or more.
70. the method for claim 68, wherein animal is people or companion animals.
71. the method for claim 68, wherein animal is old and feeble animal.
72. the method for claim 68, wherein composition further comprises one or more vitamin B group, one or more antioxidants or the two.
73. be used to increase the method for animal trainability, it comprises that the composition that will comprise LCPUFA, NORC and MCTs is applied to animal with the amount of effective increase trainability.
74. the method for claim 73, wherein animal is people or companion animals.
75. the method for claim 73, wherein animal is childhood or adults.
76. the method for claim 73, wherein animal is old and feeble animal.
77. the method for claim 73, wherein animal is feral or wildlife.
78. the method for claim 73, wherein composition further comprises one or more vitamin B group, one or more antioxidants or the two.
79. be used to keep the method for the optimum cerebral function of animal, it comprises that the composition that will comprise LCPUFA, NORC and MCTs is with effective prevention or delay the amount that cerebral function descends and be applied to animal.
80. the method for claim 79, wherein animal is people or companion animals.
81. the method for claim 79, wherein animal is childhood or adults.
82. the method for claim 79, wherein animal is old and feeble animal.
83. the method for claim 79, wherein composition further comprises one or more vitamin B group, one or more antioxidants or the two.
84. be used to promote the method for animal learning and memory, it comprises that the composition that will comprise LCPUFA, NORC and MCTs is applied to animal with the amount of effective promotion animal learning and memory.
85. the method for claim 84, wherein animal is people or companion animals.
86. the method for claim 84, wherein animal is childhood or adults.
87. the method for claim 84, wherein animal is old and feeble animal.
88. the method for claim 84, wherein composition further comprises one or more vitamin B group, one or more antioxidants or the two.
89. be used to reduce the method for animal memory loss, it comprises that the composition that will comprise LCPUFA, NORC and MCTs is applied to animal with the amount of effective minimizing memory loss in time.
90. the method for claim 89, wherein animal is people or companion animals.
91. the method for claim 89, wherein animal is old and feeble animal.
92. the method for claim 89, wherein composition further comprises one or more vitamin B group, one or more antioxidants or the two.
93. be used to delay the aging method of animal brain, it comprises that the composition that will comprise LCPUFA, NORC and MCTs is applied to animal with the amount that effectively delays aging of brain.
94. the method for claim 93, wherein animal is people or companion animals.
95. the method for claim 93, wherein animal is old and feeble animal.
96. the method for claim 93, wherein composition further comprises one or more vitamin B group, one or more antioxidants or the two.
97. be used to prevent or treat the method for animal apoplexy, it comprises that the composition that will comprise LCPUFA, NORC and MCTs is applied to animal with the amount of effective prevention or treatment apoplexy.
98. the method for claim 97, wherein animal is people or companion animals.
99. the method for claim 97, wherein animal is old and feeble animal.
100. the method for claim 97, wherein composition further comprises one or more vitamin B group, one or more antioxidants or the two.
101. be used to prevent or treat the method for animal dementia, it comprises that the composition that will comprise LCPUFA, NORC and MCTs is applied to animal with effective prevention or the dull-witted amount of treatment.
102. the method for claim 101, wherein animal is people or companion animals.
103. the method for claim 101, wherein animal is old and feeble animal.
104. the method for claim 101, wherein composition further comprises one or more vitamin B group, one or more antioxidants or the two.
105. be used to prevent or treat the method for Alzheimer disease of suffering from or easily suffering from the animal of Alzheimer disease, it comprises that the composition that will comprise LCPUFA, NORC and MCTs is applied to animal with the amount of effective prevention or treatment Alzheimer disease.
106. the method for claim 105, wherein animal is the people.
107. the method for claim 105, wherein composition further comprises one or more vitamin B group, one or more antioxidants or the two.
108. be used to strengthen the method for cognitive function of suffering from or easily suffering from the animal of Alzheimer disease, it comprises that the composition that will comprise LCPUFA, NORC and MCTs is applied to animal with the amount of effective enhancing cognitive function.
109. the method for claim 108, wherein animal is the people.
110. the method for claim 108, wherein composition further comprises one or more vitamin B group, one or more antioxidants or the two.
111. comprise composition of the present invention and the packing that invests the label on the packing, described label comprises word or phrase, picture, design, initialism, poster, phrase or other devices or their combination, and it has indicated to comprise in the described packing and has been applicable to strengthens cognitive function in animal; Change cognition, motion or ethological function; Reduce or prevention social interaction reduction; Minimizing or the prevention behavior relevant with the age changes; Increase trainability; Keep optimum cerebral function; Promote learning and memory; And/or reduce and remember the composition that loses.
112.LCPUFA, NORC and MCTs be used for strengthening cognitive function animal in preparation; Change cognition, motion or ethological function; Reduce or prevention social interaction reduction; Minimizing or the prevention behavior relevant with the age changes; Increase trainability; Keep optimum cerebral function; Promote learning and memory; And/or the application in the medicine of minimizing memory loss.
113. the application of the medicine of claim 112, it is used to prevent or treat the Alzheimer disease of suffering from or easily suffering from the animal of Alzheimer disease.
114. the application of the medicine of claim 113, wherein animal is the people.
115. the application of the medicine of claim 112, it is used to strengthen the cognitive function of suffering from or easily suffering from the animal of Alzheimer disease.
116. the application of the medicine of claim 115, wherein animal is the people.
117. the application of the medicine of claim 112, its Chinese traditional medicine further comprise one or more vitamin B group, one or more antioxidants or the two.
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